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Though often mocked, the rare exceptions to the norm can sometimes be particularly instructive. And among human chromosomes, chromosome 17 is indeed an important exception. In the April 20 issue of Nature, an international scientific team led by Ó³»­´«Ã½ researchers reports the full sequence and analysis of chromosome 17, revealing an unusual history that may help to illuminate the structural changes behind genome evolution.

When compared to its genetic brethren, chromosome 17 exhibits some remarkable qualities. With the second highest gene density of all the chromosomes, it is chock-full of protein-coding genes and houses several that are associated with human disease, such as BRCA1, a gene implicated in early onset breast cancer, and NF1, a gene involved in neurofibromatosis. The chromosome also ranks third highest among human autosomes for its load of segmental duplications — stretches of DNA that share highly similar sequences, a signature of their common origin.

Perhaps the most striking feature though, relates less to the chromosome's ranking among its human counterparts than to its stature relative to the chromosomes of the mouse. It shares its roots with just a single mouse chromosome, chromosome 11, and is the largest human autosome to have such singular origins.

Relative to their mammalian ancestors, human chromosomes typically have undergone less shuffling during the course of evolution than their mouse counterparts. But chromosome 17 is a notable exception — it has endured extensive internal rearrangements, while the corresponding region in the mouse (and in other mammals) has remained largely untouched. On the heels of this observation follows another surprising find: though the human chromosome is overflowing with segmental duplications, its genetic cousin has very few. In humans, this architecture of duplication and rearrangement has drastic consequences. It can increase the chromosome's fragility, making it prone to abnormal recombination events, and often results in the misplacement of important genetic instructions, which can lead to disease.

The scientists found a clear correlation between the locations of segmental duplications and the genetic rearrangements that have occurred in chromosome 17. A detailed comparison of the duplications' DNA sequences revealed a set of common sequence elements. These core elements led researchers to identify similar sequences in other animal genomes, and to assemble a genetic record of the chromosome's history. This analysis uncovered several noteworthy trends, which suggest that segmental duplications often multiply in a localized fashion, but expand over larger distances only after regions of a chromosome reorganize themselves. Moreover, many of the core sequence elements shared among the segmental duplications on chromosome 17 are associated with actively transcribed regions. Together, these findings indicate a potential mechanistic link between gene activity, segmental duplications and large-scale DNA rearrangements.

In the future, understanding the nuts and bolts of this connection may shed light on the structural evolution of the genome and could reveal why some chromosomes meet such different fates in distinct animal lineages. This knowledge will ultimately help scientists dissect the chromosomal basis of human genetic diversity and disease.